DESCRIPTION: (Applicant's Description) This study is designed to evaluate the independent and joint effects of serum steroid hormone concentrations and alpha fetoprotein (AFP) levels during pregnancy on the long term risk of breast cancer. Although the mechanism by which full-term pregnancy confers long term protection against breast cancer is not presently understood, experimental evidence is accumulating to implicate a protective role for the pregnancy protein AFP. Elevated levels of AFP have been hypothesized to reduce breast cancer risk by interacting with estrogen, thereby regulating the estrogen-induced proliferation of epithelial cells in the breast. This study would be the first to assess directly the combined effect of these naturally occurring substances in human serum during pregnancy and their potential for modulating breast cancer risk. The proposed study will utilize an existing data source and banked serum to conduct a case-control study nested within a cohort of pregnant women who participated in the University of California at Berkeley's Child Health and Development Studies during the period of 1959-1966. Cases (N=247) were defined as women with histologically confirmed breast carcinoma identified through the California Cancer Registry from January 1969 through June 1992. Controls (N=463) were selected from the remaining members of the cohort and probability matched to cases by age (approximately 2 to 1) using randomized recruitment. Information on major risk factors for breast cancer such as age, race, age at first full-term pregnancy, number of previous pregnancies, age at menarche, body weight, height and alcohol intake were obtained by interview questionnaire during pregnancy. In a previous study by the investigator's group, AFP levels were measured in stored sera obtained during the third trimester of the last pregnancy. Elevated AFP levels were found to reduce subsequent risk of breast cancer among women with a first full-term pregnancy before the age of 26. The present study will build on these data by measuring estradiol, estriol, estrone and progesterone from the same aliquot of serum previously assayed for serum levels of AFP. Alterations in serum levels of estrogen (estradiol, estriol, or estrone) and progesterone and estrogen:progesterone ratios will be evaluated for associations with breast cancer risk. The association between steroid hormone levels and breast cancer risk is hypothesized to differ among those with high and low serum concentrations of AFP, with hormone-associated risk attenuated among those with high AFP values.